We will study certain problems in the pathogenesis and management of herpes simplex virus (HSV) infections of the eye. Between disease episodes HSV is latent in sensory and autonomic neurons serving the eye, mainly in the trigeminal ganglion (TG) and superior cervical ganglion (SCG), but is not present in the eye itself. In animal models, we will examine the role of trauma and of local treatment of the eye with adrenergic draugs (6-hydroxydopamine, epinepherine, phenyleprine and othres) on the establishment of ganglionic infection and reactivation of latent infection associated with HSV eye infection. The effect of these drugs will be evaluated by the amount of virus in ganglia in acute infection and by the recovery of replicating virus from homogenates of latently infected ganglia, i.e. reactivation. Because HSV eye infections are the only form of herpetic infections in humans to receive repeated treatment with antiviral drugs, it is during episodes of treated eye disease that drug resistant HSV strains might be selected. We will examine various mechanism by which drug resistand HSV strains might persist between disease episodes following eye infection of experimental animals with resistant HSV strains. Because latent HSV infection has been demonstrated in some tissues (e.g. mouse uterus or guinea pig footpad) following HSV infection, we will examine the eyes of experimentally infected mice and rabbits foar evidence of latent infection. These studies will elucidate unique aspects of HSV eye infection in humans and may enable better methods to be developed for the prevention of recurrent disease episodes.